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1. Introduction
2. Controlling cancer
3. Talk outline
4. 1978: discovery of p53
5. 1979: p53 first published results
6. Co-immunoprecipitation of T-antigen and p53
7. DNA virus proteins inactivate p53 and Rb: SV40
8. DNA virus proteins inactivate p53 and Rb: Adeno
9. DNA virus proteins inactivate p53 and Rb: HPV
10. Schematic representation of the p53 protein
11. Anti-p53 Abs stain in nuclei of human cancer cells
12. Incidence of p53 mutations in human cancers
13. Crystal structure of the p53 DNA-binding region
14. What does p53 do?
15. The p53 pathway is blocked in many tumour cells
16. Negative feedback loop of p53 and HDM2
17. Mdm2 controls p53 - genetic experiments
18. Evidence for the fine regulation of the p53 response
19. How does p53 cause advanced aging?
20. Therapy approaches
21. Approval of gene therapy in China - not the U.S.
22. Activating p53
23. Blockage of p53/HDM interaction activates p53
24. Peptide minimisation and optimisation
25. Induction of p53 by peptide 7 epimer F2
26. Binding of bisarylsulfonamides to HDM2
27. Nutlin: inhibitor of the p53-MDM2 interaction
28. Nutlin 3 specificity
29. Testing compounds for their ability to activate p53
30. Summary of screening 35,000 compounds
31. CYC202: a cdk inhibitor in clinical trials
32. Tumour suppressors induce small CDK inhibitors
33. CDK inhibition
34. Specificity of CYC202 in vitro
35. CYC202 effect on tumour growth
36. Biomarkers for CYC202 p53 induction
37. Inhibition of transcription can trigger apoptosis
38. Hypothesis: activation of p53 by CYC202
39. Stress stimuli that control the activity of p53
40. New isoforms of p53
41. Jean Christophe Bourdon
42. Putative p53 protein isoforms
43. Acknowledgments (1)
44. Acknowledgments (2)

Topics Covered

• Controlling cancer
• p53 discovery
• Oncoproteins
• SV40, Adeno and HPV
• The p53 protein
• Incidence of genetic changes in p53 in human cancers
• What does p53 do?
• The p53 pathway is blocked in many tumor cells
• p53 and HDM2 are connected by a negative feedback loop
• Mdm2 controls p53
• Evidence for the fine regulation of the p53 response
• How does p53 cause advanced aging?
• Therapy approaches
• Gene therapy
• Activating p53
• Targets for p53 activation
• Small peptides block p53/HDM interaction and activate p53
• Peptide minimization and optimization
• Nutlin 3 specificity
• Thousands of compounds can be tested for their ability to activate p53-dependent transcription
• CYC202: a cdk inhibitor in clinical trial that is a non genotoxic activator of the p53 response
• CDK inhibition
• Regulation of p53 by ubiquitin like proteins
• Stress stimuli that control the activity of p53
• New isoforms of p53

Links

Series:

• The Cell Division Cycle

Categories:

• Biochemistry
• Cancer
• Cell Biology
• Clinical Medicine
• Pharmaceutical Sciences

Therapeutic Areas:

• Oncology

Talk Citation

Lane, D. (2009, June 28). Drug discovery and target validation in the p53 pathway [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved May 21, 2018, from https://hstalks.com/bs/1271/.

Talk Information

• Published on June 28, 2009